Uncovering Factors Linked to Celiac Disease
Two recent studies have provided important insights into celiac disease, including its prevalence in different areas of the United States and the possibility that a viral infection may trigger the disease in genetically susceptible people. The immune system is constantly poised to attack foreign material in the body, but, importantly, it will refrain from attacking benign substances, such as the food we ingest or the body’s own cells. In people with celiac disease, however, the immune system in the small intestine treats gluten—a protein naturally found in wheat, barley, and rye—as a foreign invader. The resulting immune response in the gut mistakenly identifies one of the body’s own proteins as foreign, damaging the intestinal lining, interfering with nutrient absorption, and leading to bloating, diarrhea, and anemia. The two genetic variants that are known to convey risk for celiac disease are very common—up to one-third of the U.S. population carries one of them. Yet only a small fraction of these people will develop the disease, meaning other genetic or non-genetic factors are likely involved.
Some studies have sought to determine whether celiac disease is more common in some geographic regions than others, which could help pinpoint factors involved in the onset of the disease. In one such recent study, scientists combed through health data from 22,277 women, men, and children living in the United States who participated in a national health survey between 2009 and 2014. The survey included questionnaires, medical histories, and blood samples, allowing the researchers to determine the number of diagnosed celiac disease cases, as well as those that were previously undiagnosed but were detected in the serological tests performed during the survey. The researchers found that people living north of latitude 40 degree North (approximately the northern border of Kansas) were over five times as likely to have celiac disease as those living south of 35 degree North (approximately the southern border of Tennessee). People living in between these latitudes were also over three times as likely to have celiac disease as people living south of the 35 degree North line. The reasons for a higher frequency of celiac disease in northern states are not clear—genetic or environmental factors could be involved—but the trend does appear to be independent of race, ethnicity, socioeconomic status, and body mass index. The scientists also found that participants who had previously undiagnosed celiac disease that was detected during the survey had lower levels of vitamin B-12 and folate in their blood, likely reflecting a deficiency in the uptake of these nutrients because of intestinal damage. This deficiency was not observed in participants with diagnosed celiac disease, underscoring the importance of diagnosing the disease and undergoing proper treatment (i.e., avoiding gluten).
Other studies have hinted that viral infections may contribute to the onset of celiac disease, but, until recently, direct evidence of a role for viruses has been lacking. A new study found that infection with a common virus, called a reovirus, may trigger celiac disease in people who are genetically susceptible to developing the disorder. People are typically exposed to reoviruses throughout their lives, but infections tend to go unnoticed because the viruses are cleared by the immune system, and any symptoms are usually mild. Nonetheless, the researchers thought that the immune responses evoked by these infections might lead to gluten intolerance in genetically susceptible people. To test this idea, the scientists first infected mice with two types of reoviruses that were originally isolated from humans, and they examined the effects on the immune systems of the mice. Both types of reoviruses infiltrated the intestinal cells, where they activated genes such as those involved in antiviral immunity. But one of the reovirus types, called T1L, evoked a more robust immune response and also activated genes in areas of the gut involved in regulating immune tolerance to ingested food. These changes appeared to disrupt the immune system by stimulating attack pathways while blocking suppression pathways, effectively interfering with the immune system’s ability to develop tolerance to certain dietary proteins. Next, the scientists sought to determine whether an immune reaction to T1L could lead to gluten intolerance in mice genetically modified to carry a human genetic variant that confers susceptibility to celiac disease. Like the experiments in the non-genetically modified mice, the scientists found that a T1L infection in these celiac disease-prone mice stimulated the immune system and prevented the mice from developing tolerance to ingested gluten. Lastly, the scientists examined plasma samples from women and men with celiac disease and found they had higher levels of antibodies to reoviruses than people without the disease, providing evidence linking celiac disease to immune responses from reovirus infections. Similarly, people with high levels of reovirus antibodies were more likely to have celiac disease.
Taken together, the results from these studies provide insight into factors that could be involved in triggering celiac disease in people who are at genetic risk, offering leads on potential approaches to disease prevention. More work along these particular lines of research could shed light onto why celiac disease is more prevalent in northern areas of the United States and whether vaccination or other antiviral approaches may be effective in preventing the disease.